Synthesis, Characterization, and Antioxidant Activities of Genistein, Biochanin A, and Their Analogues

Article abstract of DOI:10.1155/2018/4032105

A series of naturally occurring genistein (3) and biochanin A (4) compounds and their analogues were synthesized from phloroglucinol. The structures of all the synthesized compounds were established by the combined use of ¹HNMR, ¹³CNMR, IR spectral data, and mass spectrometry; their antioxidant activities were investigated. Most of the synthesized compounds show moderate-to-high activity; only two compounds exhibit no significant activity.

Full text of DOI:10.1155/2018/4032105

Hindawi
Journal of Chemistry
Volume 2018, Article ID 4032105, 6 pages
https://doi.org/10.1155/2018/4032105
Research Article
Synthesis, Characterization, and Antioxidant Activities of
Genistein, Biochanin A, and Their Analogues
Salah Hamza Sherif 1 and BerihuTekluu Gebreyohannes2
1Department of Organic Chemistry, Hawassa University, Hawassa, Ethiopia
2Department of Organic Chemistry, Foods, Drugs & Water, Andhra University, Visakhapatnam 530003, India
Correspondence should be addressed to Salah Hamza Sherif; hamzasalahsherif@gmail.com
Received 16 June 2017; Accepted 28 September 2017; Published 16 January 2018
Academic Editor: Maria B. P. P. Oliveira
Copyright © 2018 Salah Hamza Sherif and BerihuTekluu Gebreyohannes. Tis is an open access article distributed under the
Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided
the original work is properly cited.
A series of naturally occurring genistein (3) and biochanin A (4) compounds and their analogues were synthesized from phloroglu-
cinol. Te structures of all the synthesized compounds were established by the combined use of 1HNMR, 13CNMR, IR spectral data,
and mass spectrometry; their antioxidant activities were investigated. Most of the synthesized compounds show moderate-to-high
activity; only two compounds exhibit no signifcant activity.
1. Introduction
Te biological and biochemical activity, potential chemo-
preventive property, therapeutic properties, and genistein
afnity towards a large variety of molecular targets attracted
the interest of many researchers. Te number of publications
regarding the synthesis and biological evaluation of genistein
and its derivatives has increased [24–27]. Tis paper presents
the synthesis of genistein, biochanin A, and their synthetic
analogues to investigate the antioxidant activities and the
efect of various substituents on the activity of the molecule.
Isofavonoids (2) are one of the main subclasses of favonoids
(1) which contain C6-C3-C6 carbon skeleton based on 3-phe-
nylchroman [1]. Tey are widely distributed in many plants
[2, 3] and in various common foods which are particularly
abundant in seeds and other parts of leguminous plants [4, 5].
Signifcant amounts of isofavonoids were found in soybeans
[6]. Epidemiological studies show that a high consumption
of soybean derived foods correlates to a low incidence of
hormone related diseases such as cancers, osteoporosis, and
cardiovascular diseases [7]. Genistein (3) has been one of
the most widely studied natural products and has exhibited
a wide range of biological activities such as anticancer [8–
11], antioxidant [12–16], and antimicrobial activities [17, 18].
Genistein can bind to both the Estrogen Receptor alpha
2. Results and Discussion
2.1. Antioxidant Activity
2.1.1. DPPH (1,1-Diphenyl-2-picrylhydrazyl) Radical Scaveng-
ing Activity. Te DPPH radical scavenging activity of the
(ERꢀ) and the Estrogen Receptor beta (ERꢁ), although it has
a higher afnity for the ERꢁ [19], and genistein is thought
to exert its estrogenic efects through mechanisms similar to
those of estradiol [20]. Biochanin A (4) is the 4ꢀ-O-methyl
derivative of genistein and biochanin A is the predominant
isofavone found in alfalfa, Trifolium pratense, and Cicer
arietinum [21] which has an inhibitory and apoptogenic efect
on certain cancer cells such as pancreatic cancer and prostate
cancer [22, 23].
synthesized compounds was carried out according to the
method of [28]. Te in vitro antioxidant activity of the fnal
compounds 4(a–h) was evaluated by DPPH (1,1-diphenyl-
2-picrylhydrazyl) radical scavenging method. Ascorbic acid
was used as the positive control. Te DPPH radical scav-
enging activity was carried out at concentration of 100 ꢂg/ml
and the results were reported as average of three replicates.
When DPPH reacts with an antioxidant compound, the
decrease in absorbance observed because of the reaction

2
Journal of Chemistry
2
1
3
4
O
1
8
H
O
O
B
H
O
O
2
O
7
6
A
5
C
5
3
4
O
H
O
O
H
O
O
H
O
O
OCH3
3
2
1
4
Figure 1: Structure of favonoid (1), isofavonoid (2), genistein (3), and biochanin A (4).
Table 1: DPPH radical scavenging activity of the target compounds.
between antioxidant molecules and radical progresses, which
results in the scavenging of the radical by hydrogen dona-
tion. Te hydrogen donating activity measured at 517 nm
showed a signifcant relationship between concentration of
compounds and percentage of inhibition. Te structures of
favonoid, isofavonoid, genistein, and biochanin A are shown
in Figure 1.
Te DPPH radical scavenging activity was expressed as %
of inhibition and results are tabulated in Table 1. Among the
target compounds 4(a–h), the compounds 4c (86.95) and 4b
(84.89) exhibited maximum DPPH free radical scavenging
activity followed by the compounds 4g (76.36), 4e (74.77), 4f
(73.81), and 4h (65.56) which possess good radical scavenging
activity when compared with the reference standard ascorbic
acid (92.22). Te compounds 4a and 4d exhibited no signif-
cant radical scavenging activity.
Entry
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
Compound
Biochanin A (4a)
Genistein (4b)
% inhibition at 100 ꢂg/mla
>100
84.89 2.155
86.95 3.94
>100
4c
4d
4e
4f
4g
4h
74.77 1.90
73.81 1.61
76.36 1.42
65.56 1.15
92.22 2.91
Ascorbic acid
aEach value represents mean SD of three independent experiments.
the hydroxyl group on the A-ring may become a major factor
to show the activity. Compound 4h which has no hydroxyl
group exhibited radical scavenging activity (65.56 1.15).
Compounds 4e, 4f, and 4g have comparable inhibitory
2.2. Procedure. Te synthesized compounds were dissolved
in DMSO at a concentration of 100 ꢂg/ml. Ascorbic acid was
used as a reference standard. 0.004% of DPPH was freshly
prepared in methanol. 2 ml of DPPH was added to each
test tube containing 100 ꢂg/ml concentration of synthesized
compounds 4(a–h) (1 ml) and of standard solution (1 ml).
It was shaken vigorously. Tey were then allowed to stand
for 30 min at room temperature in dark place. Te control
was carried without addition of DPPH and the synthesized
compounds. DMSO was used for base line corrections and
absorbance (OD) of sample was measured at 517 nm. Te
following formula was used to interpret the value of the
sample:
activities. 4g (76.36
1.42), 4e (74.77
1.90), and 4f
(73.81 1.61) exhibited moderate activity. Te remaining
two compounds, 4a and 4d, exhibited no signifcant radical
scavenging activity.
3. Experimental Section
3.1. Materials and Methods. All chemicals and solvents were
purchased from Sigma-Aldrich and used without further
purifcation; the reaction process was monitored by TLC sil-
ica gel plates; the purifcation of the products was per-
formed using column chromatography using silica gel (100–
200 mesh). Melting points were measured in open capillary
tubes and were uncorrected; infrared (IR) spectra were
recorded using FT-IR Bruker Alpha spectrometer. NMR
spectra were recorded on Bruker (400 MHz) spectrometer
using TMS as the internal standard; mass spectra were
recorded on an Agilent 110 Lc/MSD. Elemental analyses were
performed on a Vario EL-III. Te antioxidant activity of all
the target compounds (4a–h) was investigated using DPPH
(1,1-diphenyl-2-picrylhydrazyl) radical method.
% Radical Scavenging Activity
(1)
(control OD − sample OD)
= [
] × 100.
control O.D
2.3. Conclusions. Te aim of the present work was to compare
the radical scavenging activities of genistein and its ana-
logues, which have various substituents at 4ꢀ position of B-
ring, and study the efect of these substituents on antioxidant
activity.
Te maximum inhibitory efect was exhibited by com-
pound 4c, (5,7-dihydroxy-3-phenyl-4H-chromen-4-one)
which lacks hydroxyl substituent on the B-ring, it has two
hydroxyl groups on the A-ring (at C-5 and C-7), and the
potent activity suggested that, in cases where the B-ring could
not contribute to the inhibitory activity of the isofavonoids,
3.2. Chemistry. Te titled compounds (4a–h) described in
this study were prepared as outlined in Scheme 1, according
to the literature method [29]. Te intermediate, substituted
trihydroxybenzoin (3a, 3c–g) was prepared by acylation
of phloroglucinol (1) with appropriately substituted phenyl
acetonitrile (2a, 2c–g), catalyzed by HCl gas and anhydrous

Journal of Chemistry
3
CN
HO
O
HO
OH
HO
OH
O
c
a
+
b
OH
O
OH
OH
R
R
R
4(a, c-d)
1
3(a, c-d)
2(a, c-d)
HO
O
d
4a
OH
4b
O
O
OH
Br
H3CO
e
4g
H3CO
O
4h
R, a = OMe, b = OH, c = H, d = F, e = NO2, f = CH3, g = Br
Scheme 1: Reagent and condition: (a) HCl , anhydrous ZnCl , dry Et O, 0∘C; (b) H O, refux; (c) Et O⋅BF , DMF, POCl , 60–70∘C, 4 h;
(gas)
2
2
2
2
3
3
(d) AlCl , toluene, 140∘C, 6 h; (e) DMS, K CO , Me CO, 60∘C, 2 h.
3
2
3
2
ZnCl in dry ether. Cyclization of the intermediate (3a,
Ar-H), 5.8 (s, 2H, Ar-H), 4.2 (s, 2H), 3.8 (s, 3H); 13 NMR
C
2
3c–g) with reagents of Et O⋅BF and DMF/POCl yielded
(DMSO-d , 100 MHz): ꢃ 202.6, 164.7, 164.2, 157.8, 130.5, 127.7,
2
3
3
6
the desired substituted isofavonoids in good yield. Tere
113.5, 103.6, 94.7, 54.9, 47.9; ESI-MS: ꢄ/ꢅ 275 [M + H]+.
are several reagents for the demethylation of methyl aryl
1-(2,4,6-Trihydroxyphenyl)-2-phenylethanone (3c). Yield:
ethers; we used anhydrous AlCl to synthesize genistein
3
47%, Mp: 158–161∘C; Anal. Calcd for C H O : C, 68.85; H,
(4b) from biochanin A (4a) by demethylation of 4ꢀ-O-
methyl of biochanin A. 4h was prepared by methylation of
4g using dimethyl sulphate in acetone in the presence of
K CO .
14 12
4
1
4.95; O, 26.20; found: C, 68.81; H, 4.98; O, 26.21;
NMR
H
(DMSO-d , 400 MHz,): ꢃ12.22 (s, 2H, -OH), 10.39 (s, 1H,
6
-OH), 7.31–7.19 (m, 5H, Ar-H), 5.83 (s, 2H, Ar-H), 4.35 (s,
2
3
13
2H);
NMR (DMSO-d , 100 MHz): ꢃ 202.2, 164.8, 164.2,
C
6
135.9, 129.6, 128.0, 126.1, 103.7, 94.7, 48.8; ESI-MS: ꢄ/ꢅ 245
3.3. Synthesis and Characterization
[M + H]+.
3.3.1. General Procedure for the Synthesis of Substituted
2ꢀ,4ꢀ,6ꢀ-Trihydroxydeoxybenzoins (3a, 3c–g). To a solution of
phloroglucinol (1) (5 g, 0.039 mol) and substituted phenyl
acetonitrile (2a, 2c–g) (0.044 mol), in 100 ml dry ether in an
ice-salt bath, 2 g anhydrous zinc chloride was added. A steady
stream of dry hydrogen chloride gas was passed through
the solution for 2 hrs of stirring continuously. Te mixture
was allowed to stand in refrigerator overnight and again dry
hydrogen chloride gas was passed through the mixture for
another 2 hours. Afer keeping the mixture in a refrigerator
for three days, the ether was decanted and washed twice with
ether; the solid obtained was hydrolyzed by refuxing with
100 ml 2% HCl water for 2 hours. Afer completion of the
reaction the mixture was cooled, fltered, and dried to yield
the target compounds.
2-(4-Fluorophenyl)-1-(2,4,6-trihydroxyphenyl)ethanone (3d).
Yield: 40%, Mp: 194–196∘C; Anal. Calcd for C H FO : C,
14 11
4
64.12; H, 4.23; O, 24.40; found: C, 64.07; H, 4.25; O, 24.43; 1
H
NMR (DMSO-d , 400 MHz,): ꢃ12.19 (s, 2H, -OH), 10.39 (s,
6
1H, -OH), 7.27–7.23 (m, 2H, Ar-H), 7.11 (t, J = 9.2, 2H, Ar-
H), 5.83 (s, 2H, Ar-H), 4.34 (s, 2H); 13CNMR (DMSO-d ,
6
100 MHz): ꢃ 202.0, 164.8, 164.2, 160.9 (d, 1ꢆ = 241 Hz, 1C),
CF
132.0 (d, 4ꢆ = 3 Hz, 1C), 131.4 (d, 3ꢆ = 8.0 Hz, 2C), 114.6
(d, 2ꢆCF = 2C1FHz, 2C,) 103.6, 94.7, 48.0; ESI-MS: ꢄ/ꢅ 263 [M +
CF
H]+.
1-(2,4,6-Trihydroxyphenyl)-2-(4-nitrophenyl)ethanone (3e).
Yield: 58%, Mp: 222–224∘C; Anal. Calcd for C H NO : C,
14 11
6
5.13; H, 3.83; N, 4.84; O, 33.19; found: C, 5.09; H, 3.84; N,
1
4.85; O, 33.21; H NMR (DMSO-d , 400 MHz): ꢃ 12.21 (s,
6
1-(2,4,6-Trihydroxy)-2-(4-methoxyphenyl)ethanone (3a). Yield:
2H, -OH), 10.92 (s, 1H, -OH), 8.22 (d, J = 8.8 Hz, 2H, Ar-H),
7.55 (d, J = 8.8 Hz, 2H, Ar-H), 5.89 (s, 2H, Ar-H), 4.57 (s,
52%; Mp: 190–194∘C; Anal. Calcd for C H O : C, 65.69; H,
15 14
5
1
5.15; O, 29.17; found: C, 65.62; H, 5.19; O, 29.19; H NMR
2H,); 13C NMR (DMSO-d , 100 MHz): ꢃ = 200.8, 165.1, 164.2,
6
(DMSO-d , 400 MHz): ꢃ 12.94 (s, 2 H, -OH), 10.92 (s, 1H,
146.2, 144.2, 131.1, 123.0, 103.7, 94.7, 48.83; ESI-MS: ꢄ/ꢅ 290
6
-OH), 7.2 (d, J = 8.0 Hz, 2H, Ar-H), 6.8 (d, J = 8.0 Hz, 2H,
[M + H]+.

4
Journal of Chemistry
1-(2,4,6-Trihydroxyphenyl)-2-p-tolylethanone (3f ). Yield: 56%,
Ar-H), 6.25 (d, J = 1.6 Hz, 1H, Ar-H); 13CNMR (DMSO-d ,
6
Mp: 168–170∘C; Anal. Calcd for C H O : C, 69.76; H, 5.46;
22.5 MHz): ꢃ 179.1, 164.6, 161.8, 156.2, 157.3, 147.01, 157.2,
15 14
4
O, 24.78; found: C, 69.72; H, 5.48; O, 24.80; 1H NMR (DMSO-
156.2, 147.0, 137.8, 123.10; ESI-MS: ꢄ/ꢅ 273 [M + H]+; FT-IR
(KBr, Cm−1): 3299 (O-H), 3077, (C-H aromatic), 2924 (C-H
aliphatic), 1664 (C=O).
d , 400 MHz): ꢃ 12.22 (s, 2H, -OH), 10.38 (s, 1H, -OH), 7.09
6
(s, 4H, Ar-H), 5.81 (s, 2H, Ar-H), 4.28 (s, 2H,), 3.01 (s, 3H,
CH ); 13C NMR (DMSO-d , 100 MHz): ꢃ202.5, 164.8, 164.2,
3
6
5,7-Dihydroxy-3-(4-nitrophenyl)-chroman-4-one (4e). Yield:
135.1, 132.8, 129.4, 128.6, 103.6, 94.6, 48.4, 20.6; ESI-MS: ꢄ/ꢅ
63%, Mp: 286–288∘C; Anal. Calcd: for C H NO : C, 60.21;
259 [M + H]+.
15
9
6
H, 3.03; N, 4.68; O, 32.08; found: C, 60.17; H, 3.05; N, 4.69; O,
2-(4-Bromophenyl)-1-(2,4,6-trihydroxyphenyl)ethanone (3g).
32.09; 1H NMR (DMSO-d , 400 MHz): ꢃ 12.70 (s, 1H, 5-OH),
6
Yield: 48%, Mp: 218–220∘C; Anal. Calcd. for C H BrO : C,
11.01 (s, 1H, 7-OH), 8.63 (s, 1H, 2-H), 8.32 (d, J = 8.8 Hz, 2H,
14 11
4
52.04; H, 3.43; Br, 24.73; O, 19.80; found: C, 52.01; H, 3.44; O,
Ar-H), 7.91 (d, ꢆ = 8.8 Hz, 2H, Ar-H) 6.46 (d, J = 1.6 Hz, 1H,
19.82; 1H NMR (DMSO-d , 400 MHz): ꢃ 12.12 (s, 2H, -OH),
Ar-H), 6.28 (d, J = 2 Hz, 1H, Ar-H); 13C NMR (DMSO-d ,
6
6
10.41 (s, 1H, -OH), 7.45 (d, J = 8.4 Hz, 2H, Ar-H), 7.18 (d, J =
22.5 MHz): ꢃ 179.1, 164.6, 161.9, 157.4, 156.1, 146.8, 137.9, 123.15,
8.8 Hz, 2H, Ar-H), 5.82 (s, 2H, Ar-H), 4.33 (s, 2H); 13C NMR
120.3, 104.3, 99.2; ESI-MS: ꢄ/ꢅ 300 [M + H]+.; FT-IR (KBr,
(DMSO-d , 100 MHz): ꢃ201.6, 164.9, 164.2, 135.3, 131.9, 130.8,
Cm−1): 3418 (O-H), 1654 (C=O).
6
119.4, 103.6, 94.7, 48.31; ESI-MS: ꢄ/ꢅ 323 [M + H]+.
5,7-Dihydroxy-3-tolyl-4H-chromen-4-one (4f ). Yield: 68%,
Mp: 193–195∘C; Anal. Calcd: for C H O ; C, 71.64; H, 4.51;
16 12
4
O, 23.86; found: C, 71.61; H, 4.53; O, 23.87; 1H NMR (DMSO-
3.3.2. General Procedure for the Cyclization of Substituted
2ꢀ,4ꢀ,6ꢀ-Trihydroxydeoxybenzoins (Synthesis of 4a, 4c–g).
With cooling and vigorous stirring (3 mL, 24 mmol), ether-
ated boron trifuoride was added drop wise to 8 mmol of 3a,
3c–g in 3 ml of anhydrous DMF. Te cooling was stopped
and phosphorus oxychloride (0.9 ml, 9.6 mmol) was added
dropwise; afer mixing all the components the reaction
mixture was stirred at 60–70∘C for 2 h and then poured into
acidifed water; the precipitate was fltered of and purifed by
column chromatography using hexane and ethylacetate in the
ratio of 8 : 2 as eluents.
d , 400 MHz): ꢃ 12.90 (s, 1H, 5-OH), 10.89, (s, 1H, 7-OH), 8.38
6
(s, 1H, 2-H), 7.46 (d, J = 8.0 Hz, 2H, Ar-H), 7.26 (d, J = 8.0 Hz,
2H, Ar-H), 6.40 (d, J= 2.0 Hz, 1H, Ar-H), 6.24 (d, J = 2.0 Hz,
1H, Ar-H), 2.34 (s, 3H,); 13CNMR (DMSO-d , 100 MHz): ꢃ
6
179.9, 164.5, 161.99, 157.5, 157.4, 154.5, 137.3, 128.8, 128.7, 127.8,
122.2, 104.4, 99.0, 93.7, 20.7; ESI-MS: ꢄ/ꢅ 269 [M + H]+; FT-
IR (KBr, Cm−1): 3264 (O-H), 3073, (C-H aromatic), 2921 (C-
Haliphatic), 1643 (C=O).
3-(4-Bromophenyl)-5,7-dihydroxy-4H-chromen-4-one (4g).
Yield: 66%, Mp: 212–214∘C; Anal. Calcd for C H BrO : C,
15 14
5
5,7-Dihydroxy-3-(4-methoxyphenyl)-4H-chromen-4-one (4a).
54.08; H, 2.72; Br, 23.99; O, 19.21; found: C, 54.06; H, 2.73; O,
Yield: 61%, Mp: 212–214∘C; Anal. Calcd. for C H O : C,
19.22; 1H NMR (DMSO-d , 400 MHz): ꢃ 12.79 (s, 1H, 5-OH),
16 12
5
6
67.60; H, 4.25; O, 28.14; found: C, 67.57; H, 4.27; O, 28.15; 1H
10.94, (s, 1H, 7-OH), 8.47 (s, 1H, 2-H), 7.66 (d, J = 8.8 Hz, 2H,
Ar-H), 7.55 (d, J = 8.4 Hz, 2H, Ar-H), 6.42 (d, J = 1.6 Hz, 1H,
NMR (DMSO-d , 400 MHz): ꢃ12.94 (s, 1H, 5-OH), 10.92 (s,
6
Ar-H), 6.25 (d, J = 1.6 Hz, 1H, Ar-H); 13C NMR (DMSO-d ,
1H, 7-OH), 8.38 (s, 1H, 2-H), 7.50 (d, J = 8.0 Hz, 2H, Ar-H), 7.0
(d, J = 8.0 Hz, 2H, Ar-H), 6.40 (1H, Ar-H), 5.77 (s, 1H, Ar-H),
6
100 MHz): ꢃ 179.5, 164.5, 161.9, 155.1, 131.1, 130.9, 121.3, 121.1,
99.2, 93.8; ESI-MS: ꢄ/ꢅ 332 [M + H]+.; FT-IR (KBr, Cm−1):
3374 (O-H), 3063, (C-H aromatic), 2919 (C-Haliphatic), 1657
(C=O).
3.79 (s, 3H); 13CNMR (DMSO-d , 100 MHz,): ꢃ 180.0, 164.3,
6
161.9, 159.17, 157.5, 154.2, 130.1, 122.9, 121.9, 113.7, 104.4, 99.0,
93.6, 55.1; 24; ESI-MS: ꢄ/ꢅ 285 [M + H]+; FT-IR (KBr, Cm−1):
3312 (O-H), 3007, (C-H aromatic), 2950 (C-H aliphatic), 1642
(C=O);
3.3.3. Demethylation of 4a (Preparation of 5,7-Dihydroxy-
3-(4-hydroxyphenyl)-4H-chromen-4-one) (4b). 4a (0.26 gm,
0.91 mmol) suspended in toluene (10 ml) was added to anhy-
5,7-Dihydroxy-3-phenyl-4H-chromen-4-one (4c). Yield: 76%,
Mp: 194–196∘C; Anal. Calcd. for C H O : C, 70.86; H, 3.96;
15 10
4
drous AlCl and the mixture was refuxed with string to 160∘C
O, 25.17; found: C, 70.82; H, 3.98; O, 25.19; 1H NMR (DMSO-
3
for 6 h; afer completion of reaction (monitored by TLC),
d , 400 MHz): ꢃ10.81 (s, 1H, 7-OH), 8.39 (s, 1H, 2-H), 8.0
6
the reaction mixture was cooled and poured into water and
(d, J = 8.8 Hz, 2H, Ar-H), 7.58 (d, J = 8.0 Hz, 2H, Ar-H),
6.97 (d, J = 2.0 Hz, 1H, Ar-H), 6.88 (d, J = 2 Hz, 1H, Ar-H);
acidifed with HCl acid to break the AlCl ; the solution was
3
13CNMR (DMSO-d , 22.5 MHz): ꢃ 174.3, 162.6, 157.4, 153.6,
then fltered, dried, and washed with toluene and purifed by
6
153.5, 132.1, 128.8, 127.6, 123.58; ESI-MS: ꢄ/ꢅ 255 [M + H]+;
FT-IR (KBr, Cm−1): 3198 (O-H), 3062, (C-H aromatic), 2925
(C-Haliphatic), 1626 (C=O).
column chromatography to yield 4b.
Yield: 84%, Mp: 292–294∘C; Anal. Calcd for C H O : C,
15 10
5
66.67; H, 3.73; O, 29.60; found: C, 66.62; H, 3.76; O, 29.62; 1H
NMR (DMSO-d , 400 MHz): ꢃ 12.94 (s, 1 H, 5-OH), 10.9 (s,
6
3-(4-Fluorophenyl)-5,7-dihydroxy-4H-chromen-4-one (4d).
1H, 7-OH), 9.61 (s, 1H, 4ꢀ-OH), 8.31 (s, 1H, 2-H), 7.38 (d, J =
4.0 Hz, 2H, Ar-H), 6.82 (d, J = 4.0 Hz, 2H, Ar-H), 6.39 (s, 1H,
Yield: 54%, Mp: 188–190∘C; Anal. Calcd. for C H FO : C,
15
9
4
66.18; H, 3.33; F, 6.98; O, 23.51 found: C, 66.13; H, 3.34; O,
Ar-H); 13C NMR (DMSO-d , 100 MHz): ꢃ 180.2, 164.2, 161.9,
6
23.55; 1H NMR (DMSO-d , 400 MHz): ꢃ 12.83 (s, 1H, 5-OH),
157.5, 157.4, 153.9, 130.1, 122.2, 121.20, 115.0, 104.4, 98.9, 93.6;
ESI-MS: ꢄ/ꢅ 271 [M + H]+.; FT-IR (KBr, Cm−1): 3412 (-OH),
3004, (C-H aromatic), 2933 (C-H aliphatic), 1652 (C=O).
6
10.93 (s, 1H, 7-OH), 8.44 (s, 1H, 2-H), 7.63 (t, J = 8.8 Hz, 2H,
Ar-H), 7.31 (t, J = 9.2 Hz, 2H, Ar-H), 6.42 (d, J = 1.6 Hz, 1H,

Journal of Chemistry
5
3.3.4. 3-(4-Bromophenyl)-5,7-dimethoxy-4H-chromen-4-one
(4h) (Prepared by Methylation of 4g). To a solution of 4 g
(6 mmol) in 10 mL acetone, potassium carbonate (18 mmol)
was added and then DMS (15 mmol) was added dropwise
and refuxed at 60∘C for about 2 h. Afer completion of
the reaction as indicated by TLC, the reaction mixture was
fltered and concentrated and the crude product was purifed
by column chromatography (eluent hexane : ethylacetate,
8 : 2).
[11] W.-F. Chen, M.-H. Huang, C.-H. Tzang, M. Yang, and M.-S.
Wong, “Inhibitory actions of genistein in human breast cancer
(MCF-7) cells,” Biochimica et Biophysica Acta (BBA) - Molecular
Basis of Disease, vol. 1638, no. 2, pp. 187–196, 2003.
[12] A. Arti, G. Muraleedharan, and M. Gale, “Antioxidant activities
of isofavones and their biological metabolites in a liposomal
system,” Free Radical Biology and Medicine, vol. 24, pp. 1355–
1363, 1998.
[13] C. E. Ru¨fer and S. E. Kulling, “Antioxidant activity of isofavones
and their major metabolites using diferent in vitro assays,”
Journal of Agricultural and Food Chemistry, vol. 54, no. 8, pp.
2926–2931, 2006.
[14] A. Arora, M. G. Nair, and G. M. Strasburg, “Antioxidant activ-
ities of isofavones and their biological metabolites in a liposo-
mal system,” Archives of Biochemistry and Biophysics, vol. 356,
no. 2, pp. 133–141, 1998.
[15] J. H. Mitchell, P. T. Gardner, D. B. McPhail, P. C. Morrice, A.
R. Collins, and G. G. Duthie, “Antioxidant efcacy of phytoe-
strogens in chemical and biological model systems,” Archives of
Biochemistry and Biophysics, vol. 360, no. 1, pp. 142–148, 1998.
[16] C. H. Lee, L. Yang, J. Z. Xu, S. Y. V. Yeung, Y. Huang, and Z.-
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and their glycosides,” Food Chemistry, vol. 90, no. 4, pp. 735–
741, 2005.
Yield: 80%, Mp: 174–176∘C; Anal. Calcd for C H BrO :
17 13
4
C, 56.53; H, 3.63; Br, 22.12; O, 17.72; found: C, 56.50; H, 3.64; O,
17.74; 1H NMR (DMSO-d , 400 MHz): ꢃ 7.78 (s, 1H, 2-H), 7.52
6
(d, J = 8.4 Hz, 2H, Ar-H) 7.43 (d, J = 8.4 Hz, 2H, Ar-H) 6.45 (d,
J = 2.4 Hz, 1H, Ar-H), 6.38 (d, J = 2 Hz, 1H, Ar-H), 3.93 (s, 3H),
3.89 (s, 3H); 13CNMR (DMSO-d , 100 MHz): ꢃ 174.8, 164.1,
6
161.4, 159.8, 150.4, 130.9, 125.3, 122.1, 109,8, 96.3, 96.2, 92.6,
92.5, 56.0; ESI-MS: ꢄ/ꢅ 361 [M + H]+; FT-IR (KBr, Cm−1):
3002, (C-H aromatic), 2923 (C-H aliphatic), 1657 (C=O).
Conflicts of Interest
Te authors declare that they have no conficts of interest.
[17] L.-N. Zhang, P. Cao, S.-H. Tan, W. Gu, L. Shi, and H.-L. Zhu,
“Synthesis and antimicrobial activities of 7-O-modifed genis-
tein derivatives,” European Journal of Medicinal Chemistry, vol.
43, no. 7, pp. 1543–1551, 2008.
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